尿苷二磷酸葡萄糖醛酸转移酶1A1基因单核苷酸多态性与儿童青少年非酒精性脂肪肝及血脂水平的关联

张萍萍; 宋洁云; 王辉; 王海俊

doi:10.16835/j.cnki.1000-9817.2021.09.027

尿苷二磷酸葡萄糖醛酸转移酶1A1基因单核苷酸多态性与儿童青少年非酒精性脂肪肝及血脂水平的关联

doi: 10.16835/j.cnki.1000-9817.2021.09.027

张萍萍¹,
宋洁云²,
王辉^1, ,,
王海俊^1, ,

1.
北京大学公共卫生学院妇幼卫生学系，北京 100191
2.
北京大学儿童青少年卫生研究所

基金项目:

国家自然科学基金项目 81973053

详细信息

作者简介:
张萍萍(1996-)，女，陕西宝鸡人，在读硕士，主要研究方向为儿童非酒精性脂肪性肝病的遗传易感性

通讯作者:
王辉，E-mail: huiwang@bjmu.edu.cn

王海俊，E-mail: whjun@pku.edu.cn

中图分类号: R446 R725.7
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- 被引次数: 0
出版历程
- 收稿日期: 2020-12-28
- 修回日期: 2021-03-08
- 网络出版日期: 2021-09-24
- 刊出日期: 2021-09-24

Association study between single nucleotide polymorphisms of UGT1A1 with NAFLD and serum lipids in children

1.
Department of Maternal and Child Health, School of Public Health, Peking University, Beijing(100191), China

摘要

摘要: 目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因的单核苷酸多态性(SNPs)与儿童青少年非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)和血脂水平的关系，为NAFLD的遗传机制研究提供科学依据。方法 2006—2007年在北京市海淀区3所中学和2所小学中选取1 027名7~18岁儿童青少年为研究对象, 分病例组(患NAFLD的学生162名)与对照组(非NAFLD学生865名)，由专职人员记录学生一般情况和既往病史，测量身高、体重，进行肝脏B超检查，并采集清晨空腹静脉血，测定血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和丙氨酸氨基转移酶(ALT)水平。对UGT1A1基因SNPs进行分型，分别采用二分类Logistic回归和多元线性回归分析UGT1A1基因3个SNPs与NAFLD和谷丙转氨酶(ALT)及血脂水平的关系。结果 UGT1A1基因rs10929303位点T等位基因与NAFLD的发生存在负相关(OR=0.51, 95%CI=0.32~0.83, P=0.01)。rs4148323位点A等位基因与TC水平呈负相关(B=-0.10, 95%CI=-0.19~-0.02, P=0.02)；将TC水平作分类变量进行分析时，结果与将其作为连续性变量分析类似。结论 UGT1A1基因rs10929303位点多态性与儿童青少年NAFLD相关，且rs4148323位点多态性和TC水平相关。
- 基因 /
- 脂肪肝 /
- 血脂异常 /
- 回归分析 /
- 儿童 /
- 青少年
Abstract: Objective To investigate the associations between single nucleotide polymorphisms of UDP glucuronosyltransferase Family 1 Member A1 (UGT1A1) with non-alcoholic fatty liver disease (NAFLD) and levels of serum lipids in Beijing children, and to provide scientific evidence for the study of genetic mechanism. Methods In total, 1 027 children aged 7-18 years were recruited from two primary schools and three middle schools from Haidian district of Beijing, who were randomly assigned to case group (n=162) and control group (n=865). General condition and medical history were collected by trained field health workers. Height, weight and liver ultrasound were examined. Additionally, fasting venous blood were collected to detect serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and alanine aminotransferase (ALT). The single nucleotide polymorphisms (SNPs) of UGT1A1 were genotyped. Binary logistic regression and multiple linear regression were applied to analyze the associations between three SNPs of UGT1A1 and NAFLD, ALT and levels of serum lipids. Results The SNP rs10929303 (C > T) of UGT1A1 was negatively associated with NAFLD(OR=0.51, 95%CI=0.32-0.83, P=0.01), while the SNP rs4148323 (G > A) was negatively associated with the serum level of TC (B=-0.10, 95%CI=-0.19--0.02, P=0.02); in addition, results were consistent regardless of whether the TC level was measured using a categorical variable or continuous variable. Conclusion The SNP rs10929303 of UGT1A1 is associated with NAFLD, and the SNP rs4148323 of UGT1A1 is associated with TC levels in Beijing children.
- Genes /
- Fatty liver /
- Dyslipidemias /
- Regression analysis /
- Child /
- Adolescent

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表 1 两组儿童青少年BMI及血生化指标水平比较(x ±s)

Table 1. Comparison of BMI and blood biochemical index levels between two groups(x ±s)

组别	人数	BMI/(kg·m^-2)	LnALT	TC/(mmol·L^-1)	TG/(mmol·L^-1)	LDL-C/(mmol·L^-1)	HDL-C/(mmol·L^-1)
病例组	162	26.75±3.85	2.92±0.84	4.23±0.75	1.17±0.56	2.50±0.63	1.36±0.28
对照组	865	20.72±3.61	2.35±0.65	4.09±0.67	0.87±0.36	2.17±0.54	1.54±0.31
t值		19.29	9.58	8.80	2.29	6.97	-6.82
P值		< 0.01	< 0.01	0.02	< 0.01	< 0.01	< 0.01

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表 2 UGT1A1基因SNPs与NAFLD的关联(n=1 027)

Table 2. Association between SNPs of UGT1A1 and NAFLD(n=1 027)

SNPs	效应等位基因	模型1		模型2
SNPs	效应等位基因	OR值(OR值95%CI)	P值	OR值(OR值95%CI)	P值
rs10929303	T	0.68(0.44~1.04)	0.08	0.51(0.32~0.83)	0.01
rs4148323	A	1.08(0.76~1.53)	0.66	1.19(0.80~1.76)	0.39
rs6742078	T	0.78(0.50~1.22)	0.27	0.82(0.50~1.34)	0.42
注：模型1校正年龄、性别；模型2校正年龄、性别、BMI。

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表 3 UGT1A1基因SNPs与血脂水平的关联[n=1 027，B值(B值95%CI)]

Table 3. Association between SNPs of UGT1A1 and levels of serum lipids[n=1 027, B(B 95%CI)]

SNPs	效应等位基因	TC		TG
SNPs	效应等位基因	模型1	模型2	模型1	模型2
rs10929303	T	0.03(-0.06~0.13)	0.03(-0.07~0.12)	0.02(-0.04~0.08)	-0.00(-0.06~0.06)
rs4148323	A	-0.11(-0.19~-0.02)^*	-0.10(-0.19~-0.02)^*	-0.05(-0.10~0.01)	-0.04(-0.09~0.01)
rs6742078	T	0.04(-0.06~0.14)	0.05(-0.05~0.15)	0.00(-0.06~0.06)	0.01(-0.05~0.07)

SNPs	效应等位基因	LDL-C		HDL-C
SNPs	效应等位基因	模型1	模型2	模型1	模型2
rs10929303	T	0.05(-0.03~0.13)	0.03(-0.05~0.11)	-0.02(-0.06~0.02)	-0.01(-0.05~0.04)
rs4148323	A	-0.04(-0.11~0.03)	-0.04(-0.11~0.04)	-0.02(-0.06~0.02)	-0.02(-0.06~0.01)
rs6742078	T	0.01(-0.07~0.10)	0.02(-0.06~0.11)	0.02(-0.03~0.06)	0.01(-0.03~0.05)
注：模型1校正年龄、性别；模型2校正年龄、性别、BMI；*P < 0.05。

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